IA1RODUC1IOA

Befinition of BYAL0R0NIBASE: a mucolytic enzyme that

facilitates the spieau of fluius thiough tissues by loweiing the viscosity of
hyaluionic aciu.
The hyaluronidases (EC 3.2.1.35) are a family of enzymes that
degrade hyaluronic acid.
In bumans, tbere are six associated genes,
including HYAL, HYAL, HYAL, and PH-JSPAM
Urigin of HYALURUNIDASE:International Scientific Vocabulary,
from hyuluronlc {uclJ] +-lJuxe {as in glucoxlJuxe]
First Known Use: 9










use as a drug
8y caLalyzlng Lhe hydrolysls of hyaluronan a consLlLuenL of
Lhe lnLersLlLlal barrler hyaluronldase lowers Lhe vlscoslLy of
hyaluronan Lhereby lncreaslng Llssue permeablllLy lL ls Lherefore
used ln medlclne ln con[uncLlon wlLh oLher drugs Lo speed Lhelr
dlsperslon and dellvery Common appllcaLlons are ophLhalmlc surgery
ln comblnaLlon wlLh local anesLheLlcs lL also lncreases Lhe absorpLlon
raLe of parenLeral flulds glven by hypodermoclysls and ls an ad[uncL
ln subcuLaneous urography for lmprovlng resorpLlon
of radlopaque agenLs Pyaluronldase ls also used for exLravasaLlon of
hyperosmolar soluLlons
8rand names of anlmalderlved hyaluronldase lnclude
Pydase
1M
(developed and manufacLured by rlmaharm lnc
uistiibuteu by Akoin Inc.) which has been FBA appioveu as a
thimeiosal-fiee animal-ueiiveu hyaluioniuase vitiase (ISTA
Phaimaceuticals) Amphauase (Amphastai Phaimaceuticals) anu
Wyuase. Wyuase howevei is no longei manufactuieu.
0n Becembei the FBA appioveu a synthetic (iecombinant
oi iBNA) human hyaluioniuase Bylenex (Balozyme Theiapeutics)
Role in cancei
The role of Hyaluronidases in cancer is controversial. Limited data
support a role of lysosomal hyaluronidases in metastasis, while
other data support a role in tumor suppression. Other studies
suggest no contribution, or effects independent of enzyme
activity. Non-specific inhibitors (apigenin, sulfated
glycosaminoglycans) or crude enzyme extracts have been used
to test most hypotheses, making data difficult to interpret. t has
been hypothesized that by helping degrade the extracellular
matrix (ECM) surrounding the tumor, hyaluronidases help cancer
cells escape from primary tumor masses. However, studies show
that removal of hyaluronan from tumors prevents tumor invasion.
Hyaluronidases are also thought play a role in the process
of angiogenesis, although most hyaluronidase preparations are
contaminated with large amounts of angiogeneic growth
factors.
[3]
As previously mentioned, there are six hyaluronidase
genes in the human genome, three of which can express active
hyaluronidases (HYAL1, HYAL2 and PH20).


Role in pathogenesis
Some bacteria, such as Staphylococcus aureus, Streptococcus
pyogenes, and Clostridium perfringens, produce hyaluronidase as a means
of using hyaluronan as a carbon source. t is often speculated
that Streptococcus and Staphylococcus pathogens use hyaluronidase as
a virulence factor to destroy the polysaccharide that holds animal cells
together, making it easier for the pathogen to spread through the tissues of
the host organism, but no valid experimental data are available to support
this hypothesis.


Role in feitilization
ln mosL mammallan ferLlllzaLlon hyaluronldase ls released by Lhe acrosome of
Lhe sperm cell afLer lL has reached Lhe oocyLe by dlgesLlng hyaluronan ln
Lhe corona radlaLa Lhus enabllng concepLlon Cene LargeLlng sLudles show LhaL
hyaluronldases such as P20 are noL essenLlal for ferLlllzaLlon alLhough
exogenous hyaluronldases can dlsrupL Lhe cumulus maLrlx1he ma[orlLy of
mammallan ova are covered ln a layer of granulosa cells lnLerLwlned ln an LCM
LhaL conLalns a hlgh concenLraLlon of hyaluronan When a capaclLaLed sperm
reaches Lhe ovum lL ls able Lo peneLraLe Lhls layer wlLh Lhe asslsLance of
hyaluronldase enzymes presenL on Lhe surface of Lhe sperm Cnce Lhls occurs Lhe
sperm ls capable of blndlng wlLh Lhe zona pelluclda and Lhe acrosome reacLlon
can occur.












Phaimacokinetics
Hyaluronidase is an enzyme which reduces the viscosity of ground
substance, thus making the tissues more permeable to injected fluids. t
facilitates distribution and absorption of locally injected substances. t also
promotes resorption of excess fluids and extravasated blood in the tissues.

HyaIuronidase Adverse Reactions / HyaIuronidase Side Effects
Urticaria occasional severe allergy.

Potentially Fatal: Hypersensitivity and anaphylaxis.

Precautions
Monitor
njection-site reaction Monitor patient for reactions at injection site and for adverse reactions
commonly associated with any drug coadministered with hyaluronidase.

SpeciaI Precautions
mpaired renal function. nfants, elderly. Patients with infections. Pregnancy, lactation.

Other Drug Interactions
Action potentiated by urokinase especially in the treatment of M. May increase absorption and
toxicity of local anaesthetics. Heparin, salicylates and NSADs may inhibit the spreading action
and efficacy of hyaluronidase.

Dosage
Parenteral Adjunct in hypodermoclysis
Adult: 1500 units for every 500-1000 ml of fluid for SC admin.

Parenteral
Facilitate SC/M injections
Adult: 1500 units directly added to the inj.

Parenteral
Aid in the dispersal of extravasated fluids or blood
Adult: 1500 units in 1 ml of water for inj or normal saline is injected into the affected area.

Parenteral
Aid in the diffusion of local anaesthetic in ophthalmology
Adult: 15 units/ml of local anaesthetic solution.

ncompatibility
Physical incompatibility has been reported with heparin and adrenaline, frusemide,
benzodiazepines and phenytoin.




ood(before/after)
nformation Not Available
List of Contraindications

Hyaluronidase and Pregnancy
Caution when used during pregnancy

Hyaluronidase and Lactation
Caution when used during lactation

Hyaluronidase and Other Contraindications
Hypersensitivity, malignancy. Direct application to the cornea, reduction of swelling of bites
or stings. Inj into or around infected area. IV admin; unexplained premature labour

Storage
Parenteral
Refrigerate at 2-8C.